The objective of this proposal is to foster a multidisciplinary approach for the study of neuropathic pain. The integration of different but related strategies provided by this program will result in greater scientific contributions than if each project were pursued individually. This proposal will bring together the disciplines of electrophysiology, pharmacology, and clinical trials research to investigate the mechanisms and treatment of neuropathic pain. Project I is directed at understanding thalamic mechanisms of pain sensation by examining the neural activity of cells (as well as the effects of electrical microstimulation) in the human thalamus of patients with chronic pain and those with normal sensory function. Project II examines properties of projection cells from the dorsal horn to the brainstem and hypothalamus. The focus is to determine the role of excitatory amino acids and neurokinins in production of hyperalgesia, a common sensory abnormality in neuropathic pain. Project III is directed at understanding the pathophysiology and biochemical nature of sympathetically maintained pain. Electrophysiological and pharmacological techniques will used to study catechol sensitization in nociceptors. Project IV examines the possible role of opiate analgesics in controlling a particular form of neuropathic pain (post-herpetic neuralgia). In a randomized, blinded, crossover study the efficacy of opiate analgesia will be compared to treatment with placebo, and the tricyclic antidepressant, amitriptyline. The "core" of this proposal will foster frequent interactions between clinicians and neuroscientists, and also provide for review by outside consultants. A particular strength of this project is that it will consider each level of the "pain axis" including the primary afferents, dorsal horn projection cells, thalamus, and finally the patient. This multidisciplinary yet highly focused attack on the problem of neuropathic pain will promote a synthesis of intellectual effort, and will potentially lead to new treatments.